The present invention relates to mass spectrometers.
Orthogonal acceleration time of flight (xe2x80x9coaTOFxe2x80x9d) mass spectrometers sample ions travelling in a first (axial) direction by periodically applying a sudden accelerating electric field in a second direction which is orthogonal to the first direction. Because the ions have a non-zero component of velocity in the first direction, the result of the pulsed electric field is that ions are accelerated into the field free or drift region of the time of flight mass analyser at an angle xcex8 with respect to the second direction. If the ions have an initial energy eVa in the first direction, and they are accelerated to an energy eVo in the orthogonal direction, then tan(xcex8)=(Va/Vo)0.5. For a continuous stream of ions travelling in the axial direction, all with the same energy eVa, the ion sampling duty cycle of the orthogonal acceleration time of flight mass analyser is typically of the order of 20-30% for ions having the maximum mass to charge ratio. The duty cycle is less for ions with lower mass to charge ratios. For example, if it is assumed that the length of the pusher region of the time of flight mass analyser is L1, the length of the detector is at least L1 (to eliminate unnecessary losses at the detector) and the distance between the pusher and the detector is L2, then if ions with the maximum mass to charge ratio have an mass to charge ratio mo, then the duty cycle Dcy for ions with a mass to charge ratio m is given by: Dcy=L1/(L1+L2).(m/mo)0.5. Accordingly, if L1=35 mm and L2=120 mm, then L1/(L1+L2)=0.2258. Hence the maximum duty cycle is 22.6% for ions with the maximum mass to charge ratio mo, and is correspondingly less for ions with lower mass to charge ratios.
According to a first aspect of the present invention, there is provided a mass spectrometer comprising:
an ion guide wherein in use a DC potential travels along a portion of the ion guide.
As will be explained in more detail below, the ion guide with a travelling DC wave is particularly advantageous in that all the ions preferably exit the ion guide with essentially the same velocity. The ion guide can therefore be advantageously coupled to an orthogonal acceleration time of flight mass analyser which can be operated in conjunction with the ion guide so as to have an ion sampling duty cycle of nearly 100% across the whole mass range i.e. the ion sampling duty cycle is improved by a factor of approximately xc3x975 and furthermore is substantially independent of the mass to charge ratio of the ions. This represents a significant advance in the art.
Most if not all of the electrodes forming the ion guide are connected to an AC or RF voltage supply. The resulting AC or RF electric field acts to radially confine ions within the ion guide by creating a pseudo-potential well. According to less preferred embodiments, the AC or RF voltage supply may not necessarily output a sinusoidal waveform, and according to some embodiments a non-sinusoidal RF waveform such as a square wave may be provided. Preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the electrodes are connected to both a DC and an AC or RF voltage supply.
According to the preferred embodiment, a repeating pattern of DC electrical potentials is superimposed along the length of the ion guide such as to form a periodic waveform. The waveform is caused to travel along the ion guide in the direction in which it is required to move the ions at constant velocity. In the presence of a gas the ion motion will be dampened by the viscous drag of the gas. The ions will therefore drift forwards with the same velocity as that of the travelling waveform and hence ions will exit from the ion guide with substantially the same velocity, irrespective of their mass.
The ion guide preferably comprises a plurality of segments. The ion guide is preferably segmented in the axial direction such that independent transient DC potentials can be applied, preferably independently, to each segment. The DC travelling wave potential is preferably superimposed on top of the AC or RF radially confining voltage and any constant or underlying DC offset voltage which may be applied to the segment. The DC potentials at which the various segments are maintained are preferably changed temporally so as to generate a travelling DC potential wave in the axial direction.
At any instant in time a moving DC voltage gradient is generated between segments so as to push or pull the ions in a certain direction. As the DC voltage gradient moves along the ion guide, so do the ions.
The DC voltage applied to each of the segments may be independently programmed to create a required waveform. The individual DC voltages on each of the segments are preferably programmed to change in synchronism such that the waveform is maintained but shifted in the direction in which it is required to move the ions.
The DC voltage applied to each segment may be programmed to change continuously or in a series of steps. The sequence of DC voltages applied to each segment may repeat at regular intervals, or at intervals that may progressively increase or decrease. The time over which the complete sequence of voltages is applied to a particular segment is the cycle time T. The inverse of the cycle time is the wave frequency f. The distance along the RF ion guide over which the waveform repeats itself is the wavelength xcex. The wavelength divided by the cycle time is the velocity v of the wave. Hence, the wave velocity, v=xcex/T=xcexf. Under correct operation the velocity of the ions will be equal to that of the travelling wave. For a given wavelength, the wave velocity may be controlled by selection of the cycle time. The preferred velocity of the travelling wave may be dependent on a number of parameters. Such parameters may include the range of ion masses to be analysed, the pressure and composition of the bath gas and the maximum collision energy where fragmentation is to be avoided. The amplitude of the travelling DC waveform may progressively increase or decrease towards the exit of the ion guide. Alternatively, the DC waveform may have a constant amplitude. In one embodiment the amplitude of the DC waveform grows to its full amplitude over the first few segments of the ion guide. This allows ions to be introduced and caught up by the travelling wave with minimal disruption to their sequence.
One application of the preferred ion guide is to convert a continuous ion beam into a synchronised pulsed beam of ions. The ability to be able to convert a continuous beam of ions into a pulsed beam of ions is particularly advantageous when using an orthogonal acceleration time of flight mass analyser since it allows the pulsing of an orthogonal acceleration time of flight mass spectrometer to be synchronised with the arrival of ions at the orthogonal acceleration region. The delay time between the time the ions exit the travelling wave ion guide and the pulsing of the orthogonal acceleration stage of the time of flight mass spectrometer depends on the distance to be travelled and the ion velocity. If all the ions have the same velocity, irrespective of their mass, then the ion sampling duty cycle will be optimised for all ions simultaneously, irrespective of their mass.
Another application of the preferred ion guide is to convert an asynchronous pulsed ion beam into a synchronous pulsed ion beam. The travelling wave ion guide may be used to collect and organise an essentially random series of ion pulses into a new series with which an orthogonal acceleration time of flight mass analyser may be synchronised. Again, if all the ions have the same velocity, irrespective of their mass, then the ion sampling duty cycle may be optimised for all ions simultaneously, irrespective of their mass.
Preferably, ions are not substantially fragmented within the ion guide so that all the ions received by the ion guide are essentially onwardly transmitted. The ion guide is therefore preferably not used as a fragmentation cell.
The ion guide may comprise a plurality of rod segments (i.e. electrodes which do not have apertures) or more preferably the ion guide may comprise an ion tunnel ion guide. An ion tunnel ion guide comprises a plurality of electrodes having apertures through which ions are transmitted in use. The electrodes may comprise ring, annular, plate or substantially closed loop electrodes. Preferably, at least 50%, 60%, 70%, 80%, 90% or 95% of the electrodes forming the ion guide have apertures which are substantially the same size or area.
The diameter of the apertures of at least 50% of the electrodes forming the ion guide is preferably selected from the group consisting of: (i) xe2x89xa620 mm; (ii) xe2x89xa619 mm; (iii) xe2x89xa618 mm; (iv) xe2x89xa617 mm; (v) xe2x89xa616 mm; (vi) xe2x89xa615 mm; (vii) xe2x89xa614 mm; (viii) xe2x89xa613 mm; (ix) xe2x89xa612 mm; (x) xe2x89xa611 mm; (xi) xe2x89xa610 mm; (xii) xe2x89xa69 mm; (xiii) xe2x89xa68 mm; (xiv) xe2x89xa67 mm; (xv) xe2x89xa66 mm; (xvi) xe2x89xa65 mm; (xvii) xe2x89xa64 mm; (xviii) xe2x89xa63 mm; (xix) xe2x89xa62 mm; and (xx) xe2x89xa61 mm.
According to a preferred embodiment, the ion guide may comprise a plurality of segments wherein each segment comprises a plurality of electrodes having apertures through which ions are transmitted and wherein all the electrodes in a segment are maintained at substantially the same DC potential and wherein adjacent electrodes in a segment are supplied with different phases of an AC or RF voltage. Such a segmented design simplifies the electronics associated with the ion guide.
The ion guide may consist of 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150,  greater than 150, xe2x89xa75 or xe2x89xa710 electrodes. Preferably at least 50% of the electrodes forming the ion guide are xe2x89xa63 mm, xe2x89xa62.5 mm, xe2x89xa62.0 mm, xe2x89xa61.5 mm, xe2x89xa61.0 mm or xe2x89xa60.5 mm thick. The ion guide preferably is  less than 5 cm, 5-10 cm, 10-15 cm, 15-20 cm, 20-25 cm, 25-30 cm or  greater than 30 cm long.
A gas may be introduced into the ion guide for causing the motion of ions to be dampened preferably without substantially causing fragmentation of the ions. Alternatively, the ion guide may be located within a vacuum chamber maintained at a pressure such that the motion of ions is dampened without substantially causing fragmentation of the ions. According to all embodiments of the present invention at least a portion of the ion guide is preferably maintained, in use, at a pressure selected from the group consisting of: (i) 0.0001-100 mbar; (ii) 0.001-10 mbar; (iii) 0.01-1 mbar; (iv)  greater than 0.1 mbar; 0.1 mbar; (viii)  greater than 1 mbar; (ix)  greater than 10 mbar; and (x)  less than 100 mbar. According to an embodiment the whole ion guide is maintained at such pressures. However, according to other embodiments only part of the ion guide is maintained at such pressures.
The travelling wave ion guide is preferably used at intermediate pressures between 0.0001 and 100 mbar, further preferably between 0.001 and 10 mbar, at which pressures the gas density will impose a viscous drag on the ions. The gas at these pressures will appear as a viscous medium to the ions and will act to slow the ions. The viscous drag resulting from frequent collisions with gas molecules helps to prevent the ions from building up excessive velocity. Consequently, the ions will tend to ride on the travelling DC wave rather than run ahead of the wave and execute excessive oscillations within the travelling potential wells.
The presence of the gas helps to impose a maximum velocity at which the ions will travel through the ion guide for a given field strength. The higher the gas pressure, the more frequent the ion-molecule collisions and the slower the ions will travel for a given field strength.
The energy of ions is dependent on their mass and the square of their velocity, and if fragmentation is to be avoided then it is desirable to keep the energy of the ions less than approximately 5-10 eV.
The preferred embodiment further comprises a time of flight mass analyser, preferably an orthogonal acceleration time of flight mass analyser. Time of flight mass analysers are discontinuous devices in that they are designed to receive a packet of ions rather than a continuous beam of ions. The time of flight analyser comprises a pusher and/or puller electrode which ejects packets of ions into a substantially field free or drift region wherein ions contained in a packet of ions are temporally separated according to their mass to charge ratio. The time taken for an ion to reach a detector is used to give an accurate determination of the mass to charge ratio of the ion in question.
Ions which exit the preferred ion guide can advantageously be arranged to reach the pusher and/or puller electrode of a time of flight mass analyser at substantially the same time. Since the ion guide produces a pulsed beam of ions, the repetition rate of the mass analyser may be matched to the waveform cycle time i.e. the repetition frequency of the DC waveform may be synchronised with the pusher pulses of the time of flight mass analyser to maximise the ion sampling duty cycle.
Since ions emitted from the ion guide will have substantially the same axial velocity, then ions of differing mass will have differing energies. If necessary, a slightly larger detector may be used in the time of flight mass analyser to accommodate ions having a spread of initial energies. Additionally and/or alternatively, the ions may be accelerated once they exit the ion guide almost immediately before reaching the pusher/puller region of the orthogonal acceleration time of flight mass analyser in order to reduce the relative energy spread of the ions. For sake of illustration only, if the ions emerge from the ion guide with constant velocity and have a range of energies from 1-10 eV then there is a 10:1 difference in axial energies between the most energetic ions and the least energetic ions. However, if all the ions are accelerated and given an additional 10 eV of energy, then the ions will have a range of energies from 11-20 eV and hence there will then only be a 1.8:1 difference in the spread of energies.
Either a continuous or pulsed ion source may be used. The ion source may comprise an Electrospray (xe2x80x9cESIxe2x80x9d), Atmospheric Pressure Chemical Ionisation (xe2x80x9cAPCIxe2x80x9d), Atmospheric Pressure Photo Ionisation (xe2x80x9cAPPIxe2x80x9d), Matrix Assisted Laser Desorption Ionisation (xe2x80x9cMALDIxe2x80x9d), Laser Desorption Ionisation, Inductively Coupled Plasma (xe2x80x9cICPxe2x80x9d), Electron Impact (xe2x80x9cEIxe2x80x9d) or Chemical Ionisation (xe2x80x9cCIxe2x80x9d) ion source.
According to the preferred embodiment, no additional (static) axial DC voltage gradient is required. However, according to less preferred embodiments a constant axial DC voltage gradient may be maintained along at least a portion of the ion guide. The travelling DC waveform would therefore be superimposed upon the underlying static axial DC voltage gradient. If an axial DC voltage gradient is maintained in use along at least a portion of the length of the ion guide, then an axial DC voltage difference of 0.1-0.5 V, 0.5-1.0 V, 1.0-1.5 V, 1.5-2.0 V, 2.0-2.5 V, 2.5-3.0 V, 3.0-3.5 V, 3.5-4.0 V, 4.0-4.5 V, 4.5-5.0 V, 5.0-5.5 V, 5.5-6.0 V, 6.0-6.5 V, 6.5-7.0 V, 7.0-7.5 V, 7.5-8.0 V, 8.0-8.5 V, 8.5-9.0 V, 9.0-9.5 V, 9.5-10.0 V or  greater than 10V may be maintained along a portion of the ion guide. Similarly, an axial static DC voltage gradient may be maintained along at least a portion of ion guide selected from the group consisting of: (i) 0.01-0.05 V/cm; (ii) 0.05-0.10 V/cm; (iii) 0.10-0.15 V/cm; (iv) 0.15-0.20 V/cm; (v) 0.20-0.25 V/cm; (vi) 0.25-0.30 V/cm; (vii) 0.30-0.35 V/cm; (viii) 0.35-0.40 V/cm; (ix) 0.40-0.45 V/cm; (x) 0.45-0.50 V/cm; (xi) 0.50-0.60 V/cm; (xii) 0.60-0.70 V/cm; (xiii) 0.70-0.80 V/cm; (xiv) 0.80-0.90 V/cm; (xv) 0.90-1.0 V/cm; (xvi) 1.0-1.5 V/cm; (xvii) 1.5-2.0 V/cm; (xviii) 2.0-2.5 V/cm; (xix) 2.5-3.0 V/cm; and (xx)  greater than 3.0 V/cm. A static axial DC voltage gradient may be used to help urge ions within the ion guide towards the downstream exit region of the ion guide. Alternatively, a static axial DC voltage gradient may be arranged which opposes the ions and helps to confine the ions to a region close to the travelling DC potential(s).
According to a second aspect of the present invention, there is provided a mass spectrometer comprising:
an ion source for emitting a beam of ions;
an ion guide comprising at least five electrodes having apertures for guiding the ions; and
a voltage supply for supplying a voltage wave along the electrodes for modulating the velocity of ions passing through the ion guide.
Preferably, the phase difference between two adjacent electrodes is selected from the group consisting of: (i)  less than 180xc2x0; (ii)  less than 150xc2x0; (iii)  less than 120xc2x0; (iv)  less than 90xc2x0; (v)  less than 60xc2x0; (vi)  less than 50xc2x0; (vii)  less than 40xc2x0; (viii)  less than 30xc2x0; (ix)  less than 20xc2x0; (x)  less than 15xc2x0; (xi)  less than 10xc2x0; and (xii)  less than 5xc2x0.
Preferably, the voltage wave is a ripple or other waveform which modulates the velocity of ions passing through the ion guide so that the ions emerge with substantially the same velocity.
Preferably, ions enter the ion guide as a substantially continuous beam but emerge as packets of ions due to the voltage wave.
According to a third aspect of the present invention, there is provided a mass spectrometer comprising:
an ion source;
an ion bunching device comprising a plurality of electrodes having apertures wherein trapping potentials are not applied to either the front or rear of the ion bunching device; and
a voltage supply for modulating the voltage seen by each electrode so that ions passing through the ion bunching device are urged forwards and emerge from the ion bunching device as packets of ions, each ion in the packet having substantially the same velocity.
According to a fourth aspect of the present invention, there is provided a mass spectrometer comprising:
an atmospheric pressure ion source;
an ion bunching device for receiving a substantially continuous stream of ions and for emitting packets of ions;
a voltage supply for supplying a voltage to the ion bunching device; and
a time of flight mass analyser arranged downstream of the ion bunching device for receiving packets of ions emitted by the ion bunching device;
wherein the voltage supply is arranged to supply a voltage waveform which travels along at least a part of the length of the ion bunching device, the voltage waveform causing ions to be bunched together into packets of ions.
According to a fifth aspect of the present invention, there is provided a mass spectrometer comprising:
an ion guide comprising xe2x89xa710 ring or plate electrodes having substantially similar internal apertures between 2-10 mm in diameter and wherein a DC potential voltage is arranged to travel along at least part of the axial length of the ion guide.
According to a sixth aspect of the present invention, there is provided a mass spectrometer comprising:
an ion guide comprising at least three segments,
wherein in a mode of operation:
electrodes in a first segment are maintained at a first DC potential whilst electrodes in second and third segments are maintained at a second DC potential; then
electrodes in the second segment are maintained at the first DC potential whilst electrodes in first and third segments are maintained at the second DC potential; then
electrodes in the third segment are maintained at the first DC potential whilst electrodes in first and second segments are maintained at the second DC potential;
wherein the first and second DC potentials are different.
Preferably, ions are not substantially fragmented within the ion guide.
According to a seventh aspect of the present invention, there is provided a mass spectrometer comprising:
a continuous ion source for emitting a beam of ions;
an ion guide arranged downstream of the ion source, the ion guide comprising xe2x89xa75 electrodes having apertures through which ions are transmitted in use, wherein the electrodes are arranged to radially confine ions within the apertures, wherein a travelling DC wave passes along at least part of the length of the ion guide and wherein ions are not substantially fragmented within the ion guide; and
a discontinuous mass analyser arranged to receive ions exiting the ion guide.
Preferably, an additional constant axial DC voltage gradient is maintained along at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the length of the ion guide.
Preferred ion sources such as Electrospray or APCI ion sources are continuous ion sources whereas a time of flight analyser is a discontinuous device in that it preferably requires a packet of ions. The ion guide according to the preferred embodiment is effective in essentially coupling a continuous ion source with a discontinuous mass analyser such as a time of flight mass analyser.
According to an eighth aspect of the present invention, there is provided a method of mass spectrometry, comprising:
travelling a DC potential along at least a portion of an ion guide.
According to a ninth aspect of the present invention, there is provided a mass spectrometer comprising:
an ion guide comprising a plurality of electrodes, wherein the following voltages are applied to at least five of the electrodes:
(i) an AC or RF voltage so as to radially confine ions within the ion guide;
(ii) a constant DC offset voltage; and
(iii) an additional DC voltage which varies with time.
Each of said electrodes may have substantially the same constant DC offset voltage (which may be OV or a positive or negative DC value) or alternatively at least some of the electrodes may be maintained at different DC offset voltages so that a constant axial DC voltage gradient is generated along at least part of the ion guide.
According to a tenth aspect of the present invention, there is provided a mass spectrometer comprising:
an RF ion guide having a plurality of segments;
an orthogonal acceleration time of flight mass analyser; and
a controller which generates a DC potential which travels along at least part of the RF ion guide so as to cause ions of different mass to be ejected from the ion guide with essentially the same velocity so that they arrive at the orthogonal acceleration time of flight mass analyser at essentially the same time.
According to an eleventh aspect of the present invention, there is provided a mass spectrometer comprising:
a continuous ion source;
an ion guide having a plurality of segments wherein a DC potential is progressively passed along at least some of the segments so that a DC wave having a first frequency passes along at least a portion of the ion guide; and
an orthogonal acceleration time of flight mass analyser having an injection electrode for injecting ions into a drift region, wherein the injection electrode is energised at a second frequency.
Preferably, the first frequency differs from the second frequency by less than 50%, 40%, 30%, 20%, 10%, 5%, 1% or 0.1%. According to a particularly preferred embodiment, the first frequency substantially matches the second frequency. According to other embodiments either the first frequency is substantially a harmonic frequency of the second frequency or the second frequency is substantially a harmonic frequency of the first frequency.
The DC wave may have a frequency in the range: (i) 1-5 kHz; (ii) 5-10 kHz; (iii) 10-15 kHz; (iv) 15-20 kHz; (v) 20-25 kHz; (vi) 25-30 kHz; (vii) 30-35 kHz; (viii) 35-40 kHz; (ix) 40-45 kHz; (x) 45-50 kHz; (xi) 50-55 kHz; (xii) 55-60 kHz; (xiii) 60-65 kHz; (xiv) 65-70 kHz; (xv) 70-75 kHz; (xvi) 75-80 kHz; (xvii) 80-85 kHz; (xviii) 85-90 kHz; (xix) 90-95 kHz; or (xx) 95-100 kHz. A frequency of approximately 10 kHz is particularly preferred.
Similarly, the injection electrode of the time of flight mass analyser may be energised with a frequency in the range: (i) 1-5 kHz; (ii) 5-10 kHz; (iii) 10-15 kHz; (iv) 15-20 kHz; (v) 20-25 kHz; (vi) 25-30 kHz; (vii) 30-35 kHz; (viii) 35-40 kHz; (ix) 40-45 kHz; (x) 45-50 kHz; (xi) 50-55 kHz; (xii) 55-60 kHz; (xiii) 60-65 kHz; (xiv) 65-70 kHz; (xv) 70-75 kHz; (xvi) 75-80 kHz; (xvii) 80-85 kHz; (xviii) 85-90 kHz; (xix) 90-95 kHz; or (xx) 95-100 kHz. A frequency of 5-50 kHz is preferred and a frequency of 10-40 kHz is particularly preferred.
In all embodiments of the present invention, the DC wave may have an amplitude selected from the group consisting of: (i) 0.2-0.5 V; (ii) 0.5-1 V; (iii) 1-2 V; (iv) 2-3 V; (v) 3-4 V; (vi) 4-5 V; (vii) 5-6 V; (viii) 6-7 V; (ix) 7-8 V; (x) 8-9 V; (xi) 9-10 V; (xii) 10-11 V; (xiii) 11-12 V; (xiv) 12-13 V; (xv) 13-14 V; (xvi) 14-15 V; (xvii) 15-16 V; (xviii) 16-17 V; (xix) 17-18 V; (xx) 18-19 V; and (xxii) 19-20 V. The amplitude is preferably the relative amplitude compared to any constant bias DC voltage applied to the ion guide. A relative amplitude in the range 1-15 V is preferred and asks a relative amplitude in the range of 5-10 V is particularly preferred.
Preferably, the ion guide comprises at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 segments.
Preferably, the DC wave comprises: (i) a potential barrier; (ii) a potential well; (iii) a potential well and a potential barrier; (iv) a repeating potential barrier; (v) a repeating potential well; (vi) a repeating potential well and potential barrier; or (vii) a repeating square wave.
Preferably, the DC wave has an amplitude and the amplitude: (i) remains substantially constant; (ii) decreases with time; (iii) increases with time; or (iv) varies non-linearly with time.
According to a twelfth aspect of the present invention, there is provided a method of mass spectrometry comprising:
passing ions to an RF ion guide having a plurality of segments; and
generating a DC potential which travels along at least part of the RF ion guide so as to cause ions of different mass to be ejected from the ion guide with essentially the same velocity so that they arrive at an orthogonal acceleration time of flight mass analyser at essentially the same time.